The objective of this research project is to investigate the physiogenetic basis of lymphopoiesis, reticulum cell hyperplasia and immune responses. We will use two lines of mice which were developed through selective breeding and inbreeding for difference in leukocyte production. The high (HLC) and low leukocyte count (LLC) lines differ in lymphocyte production by seven fold, as well as in a number of biological characteristics which are genetically fixed. We will study the pathology and progression of reticulum cell hyperplasia and polydypsia, both of which are characteristic of LLC mice. Examining the mice at various stages of aging for possible development of leukemia, we will test for differences between these lines, with respect to their response to carcinogens. Preliminary results indicate that HLC and LLC mice differ in immune response to heteroantigens and alloantigens; this may result from a difference in T-lymphocyte production. Such a conclusion is based, in turn, on differences in lymphoid organ weights. We will use physiological, immunological, and genetic techniques in attempting to pinpoint specific endocrine systems and major genes as the underlying influences at work. Eventually, we hope to establish a cause-and-effect relationship between these biological and pathological characteristics.